Small cell lung cancer (SCLC) accounts for approximately one fifth of all lung carcinomas, and chemotherapy remains the preferred treatment for patients with this disease. Chemotherapy regimens for SCLC have included many different compounds, cyclophosphamide, doxorubicin, methotrexate, etoposide, vincristine, cisplatin and carboplatin to name a few, but the standard treatment is a doublet of cisplatin or carboplatin with etoposide.

Adding to the compounds that are being investigated to treat SCLC, amrubicin has demonstrated potent antitumor activity, and in a phase I–II study, patients with extensive disease (ED) SCLC were treated with amrubicin plus cisplatin, and showed an overall response rate of 87.8%. The median survival time was 13.6 months, and the two year survival rate was 17.6%. In this context, the randomized phase II EORTC 08062 trial was designed to confirm the activity and safety of amrubicin alone, cisplatin and amrubicin as first line treatments in ED-SCLC in Caucasian population.[1]

The overall response rate (ORR), the primary endpoint in this trial, was assessed using the RECIST 1.0 criteria. Toxicity, progression free survival, and overall survival were secondary endpoints. Patients with previously untreated ED-SCLC, WHO performance status 0–2, and measurable disease were eligible for this trial. The trial included 33 patients in each arm, and among them there were 28 patients in the amrubicin alone arm, 30 patients in the cisplatin and amrubicin arm, and 30 patients in the cisplatin plus etoposide arm eligible patients who started treatment. ORR was 61% for the amrubicin alone arm (90% 1-sided confidence interval [CI] 47–100%), 77% for the cisplatin and amrubicin arm (CI 64–100%), and 63% for the cisplatin plus etoposide arm (CI 50–100%).

Reported grade P3 hematological toxicity in the amrubicin alone, cisplatin and amrubicin, and cisplatin plus etoposide arms were, respectively, 73%, 73%, 69% for neutropenia; 17%, 15%, 9.4% for thrombocytopenia, 10%, 15%, 3.1% for anemia, and 13%, 18%, 6% for febrile neutropenia. Early deaths, including those that were treatment related, occurred in one patient in the amrubicin alone arm, three patients in the cisplatin and amrubicin arm, and three patients in the cisplatin plus etoposide arm. No difference was observed in cardiac toxicity among the three arms.

All three regimens were active as first line treatment in patients with extensive disease; cisplatin and amrubicin met the criteria for further investigation despite slightly higher hematological toxicity, and amrubicin alone was shown to be an active and well tolerated drug.